In vivo imaging of activity-dependent synaptogenic events between dynamic axonal and dendritic filopodia within the developing brain- Connections to the development of schizophrenia and highly common …

Mounting evidence suggests that many common neurological and psychiatric disorders, such as schizophrenia, autism, and epilepsy, originate from abnormal brain circuit formation and neuron (nerve cell) growth during early development. An increasing number of studies show that in addition to genes, conditions in our surroundings can influence neuron development during early life and in later years. One important contributor to abnormal neuron growth may be altered levels of glutamate (the primary neurotransmitter that nerve cells use to send signals across synapses) and its neurotransmitting capabilities – called glutamatergic synaptic transmission. For example, a reduced glutamatergic transmission has been associated with schizophrenia and an increased level with neonatal seizures. Derek Dunfield is investigating how neurons connect with each other and how activity influences those connections during development. Specifically he is measuring the influence of glutamatergic transmission on dynamic brain circuit growth. Derek is examining real-time imaging of neurons during development using a relatively new imaging technique called two-photon microscopy and a labeling technique called single-cell electroporation. This allows him to label single neurons with different colours and watch how they interact together as they grow. Derek hopes this research will lead to better treatment and diagnosis for disabling brain disorders.

Glutamate regulation at the Drosophila larval neuromuscular junction: a model for excitatory synaptic function

The human brain is composed primarily of two cell types – neurons, which extend axons that make contact with other neurons at synapses, and glia, which wrap around neurons, protecting them and regulating their function. An electrical signal is conducted through the axon to the synapse where neurotransmitters are released to electrically excite the next neuron. The termination of this chemical signal is controlled by nearby glia, which remove the neurotransmitter using transporter proteins on their cell surfaces. A malfunction in this activity may lead to excessive levels of neurotransmitter accumulating in the synapse, over-exciting nearby neurons and glia and eventually leading to cell degeneration and death. This type of glial malfunction has been linked to many common neurodegenerative diseases (e.g. stroke, Alzheimer’s, multiple sclerosis and muscular dystrophy). Glutamate, the neurotransmitter at most brain synapses, is also present at many synapses of the fruit fly (Drosophila melanogaster). As in humans, fly glia have glutamate transporters that are thought to regulate synaptic communication. Robert Parker is studying glial neurotransmitter transporter function in the fruit fly, altering the amount of glutamate transporter present in glial cells near the Drosophila neuromuscular junction (a synapse between a neuron and a muscle cell) which may cause the over-excitation, degeneration and death of nearby cells. By studying the basic function of glutamate transporters in flies, he hopes to gain a greater understanding of the clinical importance of glutamate transporters in many human neurodegenerative diseases.

Researching knowledge transfer and exchange in occupational and environmental health

There is growing recognition that many diseases and disorders, such as asthma, joint and tendon disorders, communicable diseases and some cancers can be caused, or aggravated by workplace exposures. Occupational health is one area where the translation of research findings into new policies and increased safety in the workplace can have an immediate and profound effect on work-related injury and disease. This process, known as knowledge transfer and exchange (KTE), involves the use of research knowledge in decision-making – for individuals setting workplace safety policy, managers supervising a workforce, or employees making decisions regarding risks in the workplace. While there is widespread recognition of the importance of communicating research knowledge to those who can benefit from it, there has been little research on the KTE process within occupational settings, and how this information can be effectively communicated outside academic circles. Research that focuses on KTE as a joint effort – where the expertise of both scientists and workers is considered and recognized – has yet to be examined within occupational settings. Dr. Anne-Marie Nicol is researching the process and context by which occupational and environmental research knowledge is exchanged from research scientists to policy-makers and to employees in the workplace. Her work includes analyzing the methods that occupational and environmental scientists use to promote their research knowledge, and examining what types of information the public and policy-makers use to make decisions about risk in the workplace. This research will help develop strategies to facilitate the effective exchange of research knowledge in a timely manner to people at risk from occupational and environmental exposures, and help ensure that the information people receive is useful and appropriate to their needs.

Characterization of novel isoforms of tapasin and their function in immune modulation

A healthy immune system constantly monitors the body, helping to detect and eliminate infected cells and those that become cancerous. This system is mediated by a group of molecules called MHC Class 1, which adhere to and present a sample of the contents of a cell for scanning by T cells. T cells are specialized immune cells that are programmed to recognize and destroy abnormal or infected cells. In auto immune disease, such as Crohn’s disease, Lupus and Rheumatoid arthritis, this system breaks down and the T cells kill both abnormal cells as well as healthy ones. Robyn Seipp is researching the role of a specific molecule within the MHC Class 1 assembly pathway called tapasin. This molecule assists in the assembly and determination of which proteins are presented to the T cells on the cell surface. Her research is examining two newly discovered variants of the tapasin molecule that appear to function differently. She is studying these variants of tapasin to determine their effect on how, when and where immune responses to various pathogens or tumours are made. Results from her research will help better understand how tapasin contributes to the body’s ability to mount immune responses to pathogens and cancers while avoiding autoimmune diseases. A better understanding of their function could have important implications for vaccine design and may lead to better application of generalized tumour therapy.

Improving the treatment of posttraumatic stress disorder: A controlled evaluation of a new behavioural treatment

Posttraumatic stress disorder (PTSD) is a common consequence of life-threatening traumatic events (e.g., road traffic collisions, military combat, criminal victimization). PTSD is a severe anxiety disorder that often follows a chronic course and is associated with significant disablement. Existing PTSD treatments are only moderately effective and research is needed to find interventions that can improve treatment outcome. One potential method of improving treatment outcome for PTSD is by reducing anxiety sensitivity, which is described as a person’s fear of experiencing the physical sensations that result from anxiety (e.g. heart palpitations, dizziness) and their belief that these sensations will have harmful consequences. Anxiety sensitivity is elevated in PTSD and is associated with PTSD symptom severity. Interventions that directly target anxiety sensitivity have the potential to enhance PTSD treatment outcome. Dr. Jaye Wald is conducting the first controlled study to examine the effectiveness of interoceptive exposure therapy (IE) on PTSD. While this behavioural intervention has been shown to be effective in treating anxiety disorders, its ability to improve the outcome of existing PTSD treatments has not yet been investigated. Dr. Wald will use IE to repeatedly expose individuals to feared bodily sensations, with the goal of eventually reducing their anxiety sensitivity. Results of this research will have important practical implications for the mental health care field and for individuals with PTSD by enhancing understanding of this disorder and ultimately improving its treatment.

Characterizing the antiviral immune response in the yellow fever mosquito, Aedes aegypti

Arthropod-borne viruses (arboviruses) are viruses transmitted to plants and animals by insect vectors, such as mosquitoes and ticks. In human and animal populations around the world arboviruses such as West Nile virus continue to cause significant morbidity and mortality. To date, research efforts around these viral diseases have focused almost entirely on humans. There is however another important aspect to the disease dynamics, which has not been addressed, and that is the effect of these viruses on the insects that transmit them. The insect immune system shares many features with the human immune system yet very little is known about how insects regulate viral infections. Research has shown that arboviruses somehow evade the insect’s immune system yet are capable of transmitting the viruses to other hosts. Dawn Cooper is examining what factors viruses use to develop in insect vectors and the factors that insects use to kill viruses. Her research focuses on characterizing the immune responses expressed in response to the virus infection of Aedes aegypti, a major vector of arboviruses. Ultimately information gained through this study will identify the novel fighting components of the insect immune response which may be exploited to reduce transmission or develop drugs to treat human infections.

Involvment of Myosin V in AMPA receptor trafficking

Neurons (nerve cells) in the brain and central nervous system relay messages to each other by releasing neurotransmitters. For the message to be received, neurotransmitter receptors and associated proteins must be strategically transported to the synapse, the site of contact between neurons. Defects in the transportation of proteins is thought to affect neuronal activity and ultimately may lead to neurological impairments like epilepsy and mental retardation. Marie-France Lise is studying this fundamental process – how the molecules important for normal brain functions are transported throughout the neurons from their site of synthesis to their specific site of action. Her research focuses on a family of neuronal proteins known as Myosin V, thought to be important regulators of protein transport. These proteins act as molecular motors by binding and “walking” cargoes along actin filament highways, leading to different destinations within the cell. By characterizing how the Myosin V family regulates transport of proteins in neurons, Marie-France hopes to gain a better understanding of how synapses are formed during brain development, learning, and memory formation.

Cardiovascular disease risk in patients with spinal cord injury before and after exercise rehabilitation

Eighty percent of spinal cord injuries happen to people under 30 years of age. Medical advances have increased life expectancy for these individuals, and consequently, they are susceptible to the same chronic conditions as able-bodied persons. However, people with spinal cord injuries have a much higher risk for cardiovascular disease. About 25 percent of the general population has a form of cardiovascular disease, but 60 to 70 percent of people with spinal cord injuries have a form of the disease. Physical inactivity is a major risk factor for cardiovascular disease, and people with spinal cord injury are often inactive and have poor cardiovascular fitness. Dominik Zbogar is investigating whether an arm cycling training program could improve aerobic fitness, heart function, muscle function, vascular (blood vessel) health, and psychological well-being in people with spinal cord injuries. This research could clarify the importance of exercise rehabilitation to overall health and quality of life for people with spinal cord injuries, and contribute to prevention and treatment of cardiovascular disease.

The role of specific genomic alterations in the aggressive nature of small cell lung cancer

Lung cancer remains the leading cause of cancer death for both men and women in Canada and Small Cell Lung Cancer (SCLC) accounts for about 25% of all cases annually. Patients diagnosed with SCLC have a very poor prognosis, with statistics indicating that only 10% of patients will survive past 5 years. This survival rate has seen little improvement over the past several decades and new targets for therapy and diagnosis of SCLC are desperately needed. SCLC is particularly challenging for researchers because samples are relatively difficult to obtain. Because the type of cell from which SCLC develops is not known, it is also difficult to define normal gene expression (RNA) levels for comparison. Bradley Coe is investigating SCLC gene expression levels by focussing on changes found in the DNA rather than in the RNA. Analysis of DNA has a significant advantage in that the source cell is not needed for establishing a baseline. Bradley is comparing the DNA profiles of SCLC cells with profiles generated from similar types of lung cancer which are less aggressive – an approach that has been made possible because of new genome comparison technology. The results of his research will include a list of genes which may contribute to the aggressiveness of SCLC. His research will also contribute to increased knowledge of the biology of SCLC, which will assist in the classification and diagnosis of this disease and in the identification of potential new targets for drug therapy.